Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma.

A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previous studies have found that adolescents with obesity-related asthma presented upregulation of RORC, IL17A, and TNFA. However, the mechanisms that cause these higher mRNA expression levels in this asthmatic phenotype are poorly understood. Methylation directly regulates gene expression by adding a methyl group to carbon 5 of dinucleotide CpG cytosine. Thus, we evaluated the relationship between RORC, IL17A, and TNFA methylation status and mRNA expression levels to investigate a possible epigenetic regulation. A total of 102 adolescents (11-18 years) were studied in the following four groups: 1) healthy participants (HP), 2) allergic asthmatic participants (AAP), 3) obese participants without asthma (OP), and 4) non-allergic obesity-related asthma participants (OAP). Real-time qPCR assessed the methylation status and gene expression levels in peripheral blood leukocytes. Remarkably, the OAP and AAP groups have lower promoter methylation patterns of RORC, IL17A, and TNFA than the HP group. Notably, the OAP group presents lower RORC promoter methylation status than the OP group. Interestingly, RORC promoter methylation status was moderately negatively associated with gene expression of RORC (r s = -0.39, p < 0.001) and IL17A (r s = -0.37, p < 0.01), respectively. Similarly, the promoter methylation pattern of IL17A was moderately negatively correlated with IL17A gene expression (r s = -0.3, p < 0.01). There is also a moderate inverse relationship between TNFA promoter methylation status and TNFA gene expression (r s = -0.3, p < 0.01). The present study suggests an association between lower RORC, IL17A, and TNFA gene promoter methylation status with obesity-related asthma and allergic asthma. RORC, IL17A, and TNFA gene promoter methylation patterns are moderately inversely correlated with their respective mRNA expression levels. Therefore, DNA methylation may regulate RORC, IL17A, and TNF gene expression in both asthmatic phenotypes.

Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents.

BACKGROUND: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified. OBJECTIVE: To evaluate RBP4 and PAI-1 as prognostic biomarkers of non-allergic asthma caused by obesity. METHODS: A cross-sectional study between four groups of adolescents: (1) healthy (n = 35), (2) allergic asthma without obesity (n = 28), (3) obesity without asthma (n = 33), and (4) non-allergic asthma with obesity (n = 18). RESULTS: RBP4 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (39.2 ng/mL [95% confidence interval (CI): 23.8-76.0] vs. 23.5 ng/mL [95% CI: 3.2-33.5], p < 0.01), and PAI-1 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (21.9 ng/mL [95% CI: 15.7-26.5] vs. 15.9 ng/mL [95% CI: 9.4-18.2], p < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the serum RBP4 cut-off value was >42.78 ng/mL, with an area under the ROC curve (AUC) of 0.741 (95% CI: 0.599-0.853, p = 0.001), considered acceptable. The PAI-1 cut-off value was >12.0 ng/mL, with an AUC of 0.699 (95% CI: 0.554-0.819, p = 0.008), considered fair. CONCLUSIONS: RBP4 may be useful to predict non-allergic asthma among obese adolescents in clinical practice.

Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents

Background: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified. Objective: To evaluate RBP4 and PAI-1 as prognostic biomarkers of non-allergic asthma caused by obesity. Methods: A cross-sectional study between four groups of adolescents: (1) healthy (n = 35), (2) allergic asthma without obesity (n = 28), (3) obesity without asthma (n = 33), and (4) non-allergic asthma with obesity (n = 18). Results: RBP4 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (39.2 ng/mL [95% confidence interval (CI): 23.8–76.0] vs. 23.5 ng/mL [95% CI: 3.2–33.5], p < 0.01), and PAI-1 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (21.9 ng/mL [95% CI: 15.7–26.5] vs. 15.9 ng/mL [95% CI: 9.4–18.2], p < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the serum RBP4 cut-off value was >42.78 ng/mL, with an area under the ROC curve (AUC) of 0.741 (95% CI: 0.599–0.853, p = 0.001), considered acceptable. The PAI-1 cut-off value was >12.0 ng/mL, with an AUC of 0.699 (95% CI: 0.554–0.819, p = 0.008), considered fair Conclusions: RBP4 may be useful to predict non-allergic asthma among obese adolescents in clinical practice (AU)

Associations of TNFA, IL17A, and RORC mRNA expression levels in peripheral blood leukocytes with obesity-related asthma in adolescents.

Obesity is associated with a unique non-T2 asthma phenotype, characterised by a Th17 immune response. Retinoid-related orphan receptor C (RORC) is the master transcription factor for Th17 polarisation. We investigated the association of TNFA, IL17A, and RORC mRNA expression levels with the non-T2 phenotype. We conducted a cross-sectional study in adolescents, subdivided as follows: healthy (HA), allergic asthma without obesity (AA), obesity without asthma (OB), and non-allergic asthma with obesity (NAO). TNFA, IL17A, and RORC mRNA expression in peripheral blood leukocytes were assessed by RT-PCR. NAO exhibited higher TNFA mRNA expression levels than HA or OB, as well as the highest IL17A and RORC mRNA expression levels among the four groups. The best biomarker for discriminating non-allergic asthma among obese adolescents was RORC mRNA expression levels (area under the curve: 0.95). RORC mRNA expression levels were associated with the non-T2 asthma phenotype, hinting at a therapeutic target in obesity-related asthma.

Measles outbreak during the COVID-19 pandemic in Mexico.

Measles is an exanthematous disease caused by a virus of the Morbillivirus genus. On February 23, 2020, the exanthema began in the first confirmed case of measles this year. At the same time, on February 28, 2020, the first case of the new coronavirus disease (COVID-19) was confirmed. Up to June 6, 2020, 176 measles cases have been confirmed: 137 in Mexico City, 37 in the state of Mexico, and two in the state of Campeche. In Mexico City, municipalities with more cases were Gustavo A. Madero, Miguel Hidalgo, and Iztapalapa; in the State of Mexico were Ecatepec, Tlalnepantla, and Netzahualcoyotl; in Campeche, there are only two cases reported. On the other hand, 7,065,133 cases of COVID-19 have been registered worldwide with a global case fatality rate of 5.7%. In Mexico, there have been 113,619 confirmed cases and 13,511 deaths, while in Mexico City, there have been 30,223 cases and 3062 deaths. Iztapalapa and Gustavo A. Madero are the locations with more cases reported. Hence, a campaign of social distancing started as part of the strategies to control the spread of the infection. The potential threat is that as social confinement measures are relaxed and mobility is initiated, both viruses could continue to spread. It is expected that due to the time that has passed since the last reported measles case, control of this disease will be achieved.

El sarampión es una enfermedad exantemática causada por un virus del género Morbilivirus. El 23 de febrero de 2020 inició el exantema en el primer caso confirmado en este año; el 28 de febrero de 2020 se confirmó el primer caso de enfermedad por un nuevo coronavirus (COVID-19). Hasta el 6 de junio de 2020 se han confirmado 176 casos de sarampión: 137 en la Ciudad de México, 37 en el Estado de México y 2 en Campeche. En la Ciudad de México, las alcaldías con más casos son Gustavo A. Madero, Miguel Hidalgo e Iztapalapa; en el Estado de México, la mayoría de los casos se presentan en Ecatepec, Tlalnepantla y Netzahualcóyotl; en el estado de Campeche solo se han reportado dos casos. Hasta el 6 de junio de 2020 se habían registrado en todo el mundo 7,065,33 casos de COVID-19, con una letalidad global del 5.7%. En México se han presentado 113,619 casos confirmados y 13,511 muertes; de ellos, 30,223 casos y 3,062 muertes en la Ciudad de México, siendo las alcaldías de Iztapalapa y Gustavo A. Madero las que han tenido el mayor número de casos. Como parte de las estrategias para controlar la diseminación de la infección, se decidió iniciar la campaña de distanciamiento social. La amenaza latente es que, al disminuir las medidas de confinamiento social e iniciar la movilidad paulatina, podrían continuar diseminándose ambos virus. Se espera que debido al tiempo transcurrido desde el último caso de sarampión reportado se logre el control de esta enfermedad.

Measles outbreak during the COVID-19 pandemic in Mexico / Brote de sarampión durante la pandemia de COVID-19 en México

Abstract Measles is an exanthematous disease caused by a virus of the Morbillivirus genus. On February 23, 2020, the exanthema began in the first confirmed case of measles this year. At the same time, on February 28, 2020, the first case of the new coronavirus disease (COVID-19) was confirmed. Up to June 6, 2020, 176 measles cases have been confirmed: 137 in Mexico City, 37 in the state of Mexico, and two in the state of Campeche. In Mexico City, municipalities with more cases were Gustavo A. Madero, Miguel Hidalgo, and Iztapalapa; in the State of Mexico were Ecatepec, Tlalnepantla, and Netzahualcoyotl; in Campeche, there are only two cases reported. On the other hand, 7,065,133 cases of COVID-19 have been registered worldwide with a global case fatality rate of 5.7%. In Mexico, there have been 113,619 confirmed cases and 13,511 deaths, while in Mexico City, there have been 30,223 cases and 3062 deaths. Iztapalapa and Gustavo A. Madero are the locations with more cases reported. Hence, a campaign of social distancing started as part of the strategies to control the spread of the infection. The potential threat is that as social confinement measures are relaxed and mobility is initiated, both viruses could continue to spread. It is expected that due to the time that has passed since the last reported measles case, control of this disease will be achieved.

Resumen El sarampión es una enfermedad exantemática causada por un virus del género Morbilivirus. El 23 de febrero de 2020 inició el exantema en el primer caso confirmado en este año; el 28 de febrero de 2020 se confirmó el primer caso de enfermedad por un nuevo coronavirus (COVID-19). Hasta el 6 de junio de 2020 se han confirmado 176 casos de sarampión: 137 en la Ciudad de México, 37 en el Estado de México y 2 en Campeche. En la Ciudad de México, las alcaldías con más casos son Gustavo A. Madero, Miguel Hidalgo e Iztapalapa; en el Estado de México, la mayoría de los casos se presentan en Ecatepec, Tlalnepantla y Netzahualcóyotl; en el estado de Campeche solo se han reportado dos casos. Hasta el 6 de junio de 2020 se habían registrado en todo el mundo 7,065,33 casos de COVID-19, con una letalidad global del 5.7%. En México se han presentado 113,619 casos confirmados y 13,511 muertes; de ellos, 30,223 casos y 3,062 muertes en la Ciudad de México, siendo las alcaldías de Iztapalapa y Gustavo A. Madero las que han tenido el mayor número de casos. Como parte de las estrategias para controlar la diseminación de la infección, se decidió iniciar la campaña de distanciamiento social. La amenaza latente es que, al disminuir las medidas de confinamiento social e iniciar la movilidad paulatina, podrían continuar diseminándose ambos virus. Se espera que debido al tiempo transcurrido desde el último caso de sarampión reportado se logre el control de esta enfermedad.

IL-17A and TNF-α as potential biomarkers for acute respiratory distress syndrome and mortality in patients with obesity and COVID-19.

Coronavirus disease 2019 (COVID-19) was declared a pandemic and international health emergency by the World Health Organization. Patients with obesity with COVID-19 are 7 times more likely to need invasive mechanical ventilation than are patients without obesity (OR 7.36; 95% CI: 1.63-33.14, p = 0.021). Acute respiratory distress syndrome (ARDS) is one of the main causes of death related to COVID-19 and is triggered by a cytokine storm that damages the respiratory epithelium. Interleukins that cause the chronic low-grade inflammatory state of obesity, such as interleukin (IL)-1ß, IL-6, monocyte chemoattractant peptide (MCP)-1, and, in particular, IL-17A and tumour necrosis factor alpha (TNF-α), also play very important roles in lung damage in ARDS. Therefore, obesity is associated with an immune state favourable to a cytokine storm. Our hypothesis is that serum concentrations of TNF-α and IL-17A are more elevated in patients with obesity and COVID-19, and consequently, they have a greater probability of developing ARDS and death. The immunobiology of IL-17A and TNF-α opens a new fascinating field of research for COVID-19.

Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: A noninferiority multicenter randomized clinical trial.

BACKGROUND: It has been suggested that low-risk febrile neutropenia (FN) episodes can be treated in a step-down manner in the outpatient setting. This recommendation has been limited to implementation in middle-income countries due to concerns about infrastructure and lack of trained personnel. We aimed to determine whether early step-down to oral antimicrobial outpatient treatment is not inferior in safety and efficacy to inpatient intravenous treatment in children with low-risk FN. PROCEDURE: A noninferiority randomized controlled clinical trial was conducted in three hospitals in Mexico City. Low-risk FN was identified in children younger than 18 years. After 48 to 72 hours of intravenous treatment, children were randomly allocated to receive outpatient oral treatment (experimental arm, cefixime) or to continue inpatient treatment (standard of care, cefepime). Daily monitoring was performed until neutropenia resolution. The presence of any unfavorable clinical outcome was the endpoint of interest. We performed a noninferiority test for comparison of proportions. RESULTS: We identified 1237 FN episodes; 117 cases were randomized: 60 to the outpatient group and 57 for continued inpatient treatment. Of the FN episodes, 100% in the outpatient group and 93% in the inpatient group had a favorable outcome (P < 0.001). The mean duration of antibiotics was 4.1 days (SD 2.5; 95% CI, 3.4-4.8 days) in the outpatient group and 4.4 days (SD 2.5; 95% CI, 3.7-5.0 days) in the inpatient group (P = 0.70). CONCLUSIONS: In our population, step-down oral outpatient treatment of low-risk FN was as safe and effective as inpatient intravenous treatment. Clinical Trials Identifier: NCT04000711.

Serological and molecular study of Hepatitis E virus in pediatric patients in Mexico.

INTRODUCTION AND OBJECTIVES: Cases of viral hepatitis reported in Mexico are typically identified as hepatitis A, B and C. However, unspecified cases are reported annually. Hepatitis E virus (HEV) is an emergent agent that causes a self-limiting infection that can evolve to chronic in immunosuppressed individuals. In Mexico, HEV genotype 2 is considered endemic, though it's the prevalence is not well known. Therefore, the present study was designed to determine the prevalence of HEV among patients at the "Hospital Infantil de Mexico Federico Gomez". MATERIALS AND METHODS: The study included 99 patients, anti-HEV antibody (IgG and IgM) were detected by indirect ELISA and viral genome was identified using RT-PCR technique. Two PCR products of positive cases were sequenced. RESULTS: ELISA results were positive in 3% and 6%, for IgG and IgM respectively, 54.5% prevalence was found by PCR. Low lymphocyte count (p<0.05) and malnutrition (p<0.005) were significant factors for high PCR prevalence and could increase the possibility of infection. Two samples were sequenced and confirmed the presence of HEV genotype 3. CONCLUSIONS: This report reveals the incidence of HEV in pediatric patients in Mexico. Moreover, the identification of HEV genotype 3 in human samples suggests a potential zoonotic risk that requires further research.

Decreased methylation profiles in the TNFA gene promoters in type 1 macrophages and in the IL17A and RORC gene promoters in Th17 lymphocytes have a causal association with non-atopic asthma caused by obesity: A hypothesis.

Obesity is a serious public health problem worldwide and has been associated in epidemiological studies with a unique type of non-atopic asthma, although the causal association of asthma and obesity has certain criteria, such as the strength of association, consistency, specificity, temporality, biological gradient, coherence, analogy and experimentation; nevertheless, the biological plausibility of this association remains uncertain. Various mechanisms have been postulated, such as immunological, hormonal, mechanical, environmental, genetic and epigenetic mechanisms. Our hypothesis favours immunological mechanisms because some cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin (IL)-17A, are responsible for orchestrating low-grade systemic inflammation associated with obesity; however, these cytokines are regulated by epigenetic mechanisms, such as gene promoter methylation.

Clinical Significance of Fractional Anisotropy Measured in Peritumoral Edema as a Biomarker of Overall Survival in Glioblastoma: Evidence Using Correspondence Analysis.

INTRODUCTION: Fractional anisotropy (FA), a diffusion tensor image (DTI) derived biomarker is related to invasion, infiltration, and extension of glioblastoma (GB). We aimed to evaluate FA values and their association with intervals of overall survival (OS). MATERIALS AND METHODS: Retrospective study conducted in 36 patients with GB included 23 (63.9%) males, 46 ± 14 y; and 13 (36.1%) females, 53 ± 13; followed up for 36 months. We measured FA at edema, enhancing rim, and necrosis. We created two categorical variables using levels of FA and intervals of OS to evaluate their relationships. Kaplan-Meier method and correspondence analysis evaluated the association between OS (grouped in 7 six-month intervals) and FA measurements. RESULTS: Median FA values were higher in healthy brain regions (0.351), followed by peritumoral edema (0.190), enhancing ring (0.116), and necrosis (0.071). Pair-wise comparisons among tumor regions showed a significant difference, P < 0.001. The median OS for all patients was 19.3 months; variations in the OS curves among subgroups was significant χ2 (3) = 8.48, P = 0.037. Correspondence analysis showed a significant association between FA values in the edema region and the survival intervals χ2 (18) = 30.996, P = 0.029. CONCLUSIONS: Alternative multivariate assessment using correspondence analysis might supplement the traditional survival analysis in patients with GB. A close follow-up of the variability of FA in the peritumoral edema region is predictive of the OS within specific six-month interval subgroup. Further studies should focus on predictive models combining surgical and DTI biomarkers.

PIPERACILLIN/TAZOBACTAM IN CONTINUOUS INFUSION VERSUS INTERMITTENT INFUSION IN CHILDREN WITH FEBRILE NEUTROPENIA.

Background: Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective: The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/tazobactam (TZP) in febrile neutropenic pediatric patients. Methods: This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results: There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions: There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

Piperacillin/tazobactam in continuous infusion versus intermittent infusion in children with febrile neutropenia

Abstract Background Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/tazobactam (TZP) in febrile neutropenic pediatric patients. Methods This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

La obesidad y el genotipo ahorrador. Determinismo biológico y social versus libre albedrío / Obesity and thrifty genotype. Biological and social determinism versus free will

Resumen La obesidad es un problema de salud pública mundial con un crecimiento alarmante para el cual no se han encontrado respuestas concluyentes en relación con sus causas. Entre las múltiples hipótesis que intentan explicar la epidemia, se encuentra la del genotipo ahorrador, propuesta por James V. Neel en 1962. Neel propone que las variaciones genéticas en comunidades cazadoras-recolectoras que fueron selectivamente favorables en el pasado -ya que permitieron enfrentar episodios de hambruna-, se convierten en una desventaja en la actualidad cuando los alimentos se han vuelto abundantes y son relativamente constantes. A pesar de tener muchos críticos, la conjetura de Neel permanece vigente. En este artículo se argumenta que la hipótesis del genotipo ahorrador apoya un enfoque explicativo basado en el determinismo biológico. Esta postura, al igual que la del determinismo social, subestiman el papel del individuo como un ente libre y responsable. Se hace la consideración de que la pandemia de obesidad no podrá ser explicada ni resuelta en tanto no ocurra un cambio drástico en el marco teórico prevalente en el que se incorpore el enfoque de que el individuo es un agente independiente, libre y responsable de sí mismo, con la capacidad potencial de colocarse por encima de su herencia biológica y del ambiente que lo rodea. No se rechaza la influencia de la biología y el entorno social en la conducta, pero se propone que esta se deriva de manera primordial de decisiones fundadas en el libre albedrío, el cual no está determinado ni biológica ni socialmente.

Abstract Obesity is a global public health problem with a concerning increasing rate and no conclusive answer related to its causes. The thrifty genotype, proposed by James V. Neel in 1962, is one of the many hypotheses that intend to explain the epidemic. Neel proposed that genetic variations in hunter-gatherer communities-which were selectively favorable in the past since they allowed to confront famine-are currently a disadvantage because food is plentiful and relatively constant. This conclusion remains valid despite being highly criticized. This review discusses that the hypothesis of the thrifty genotype supports an explicative approach based on biological determinism. This approach, such as social determinism, underestimates the role of individuals as free entities responsible for their own behavior. While a drastic change in the current theoretical framework occurs, in which individuals are considered as independent, free and self-responsible agents with the ability to overcome their heredity and their environment, the idea that the obesity pandemic cannot be explained or solved will be present. Although the influence of these elements in behavior is not rejected, it is proposed that behavior potentially and mainly comes from free will, which is neither biologically nor socially determined.

Obesity and thrifty genotype. Biological and social determinism versus free will.

Obesity is a global public health problem with a concerning increasing rate and no conclusive answer related to its causes. The thrifty genotype, proposed by James V. Neel in 1962, is one of the many hypotheses that intend to explain the epidemic. Neel proposed that genetic variations in hunter-gatherer communities-which were selectively favorable in the past since they allowed to confront famine-are currently a disadvantage because food is plentiful and relatively constant. This conclusion remains valid despite being highly criticized. This review discusses that the hypothesis of the thrifty genotype supports an explicative approach based on biological determinism. This approach, such as social determinism, underestimates the role of individuals as free entities responsible for their own behavior. While a drastic change in the current theoretical framework occurs, in which individuals are considered as independent, free and self-responsible agents with the ability to overcome their heredity and their environment, the idea that the obesity pandemic cannot be explained or solved will be present. Although the influence of these elements in behavior is not rejected, it is proposed that behavior potentially and mainly comes from free will, which is neither biologically nor socially determined.

La obesidad es un problema de salud pública mundial con un crecimiento alarmante para el cual no se han encontrado respuestas concluyentes en relación con sus causas. Entre las múltiples hipótesis que intentan explicar la epidemia, se encuentra la del genotipo ahorrador, propuesta por James V. Neel en 1962. Neel propone que las variaciones genéticas en comunidades cazadoras-recolectoras que fueron selectivamente favorables en el pasado ­ya que permitieron enfrentar episodios de hambruna­, se convierten en una desventaja en la actualidad cuando los alimentos se han vuelto abundantes y son relativamente constantes. A pesar de tener muchos críticos, la conjetura de Neel permanece vigente. En este artículo se argumenta que la hipótesis del genotipo ahorrador apoya un enfoque explicativo basado en el determinismo biológico. Esta postura, al igual que la del determinismo social, subestiman el papel del individuo como un ente libre y responsable. Se hace la consideración de que la pandemia de obesidad no podrá ser explicada ni resuelta en tanto no ocurra un cambio drástico en el marco teórico prevalente en el que se incorpore el enfoque de que el individuo es un agente independiente, libre y responsable de sí mismo, con la capacidad potencial de colocarse por encima de su herencia biológica y del ambiente que lo rodea. No se rechaza la influencia de la biología y el entorno social en la conducta, pero se propone que esta se deriva de manera primordial de decisiones fundadas en el libre albedrío, el cual no está determinado ni biológica ni socialmente.